Abstract: OBJECTIVE To study the protective effect and mechanism of safflower extract(SE) on cardiac ischemia reperfusion injury(IRI) in rats. METHODS Fifty SD rats were randomly divided into 5 groups(n=10):sham group, IRI group, and SE 1, 2, 4 g·kg^-1 group(equivalent to raw material). Rats in the sham group and IRI group received saline at 30 min before operation(1 mL, intraperitoneally), SE groups received corresponding dose of SE by intraperitioneal injection. The IRI and SE groups were clamped the left anterior descending coronary artery, and removed the clamp for reperfusion after 30 min. After surgery, the ±dp/dtmax, LVDP, LVEDP, HR of these rats were measured. Restore heart perfusion for 20 min, the rats were sacrificed and collected the myocardial tissues and serum, measured the structures and the area of myocardial infarction. Furthermore, CK-MB, LDH, Akt, p-Akt, PI3K, m-TOR, NF-κB, IL-6, TNF-α levels were evaluated. RESULTS Compared with sham group, the HR, LVDP, ±dp/dtmax, LVEDP were decreased and CK-MB, LDH, Akt, p-Akt, PI3K, m-TOR, NF-κB, IL-6, TNF-α levels were decreased especially in the IRI group. The heart pathological structure had a significant change in the IRI group. Compared with the IRI group, the level of the HR, LVDP, ±dp/dtmax, LVEDP were increased, CK-MB, LDH, NF-κB, IL-6, and TNF-α were increased in SE group. Moreover, the level of the Akt, p-Akt, PI3K and m-TOR were significantly increased. The changes of heart pathological structure was depressed. CONCLUSION SE can protect on cardiac IRI in a dose-dependent manner, and its mechanism related to activat the PI3K/m-TOR signaling pathway, and inhibit the release of inflammatory factors.